title: Myocardial extravascular extracellular volume fraction measurement by gadolinium cardiovascular magnetic resonance in humans: slow infusion versus bolus.
abstract: BACKGROUND
  Myocardial extravascular extracellular volume fraction (Ve) measures quantify diffuse fibrosis not readily detectable by conventional late gadolinium (Gd) enhancement (LGE). Ve measurement requires steady state equilibrium between plasma and interstitial Gd contrast. While a constant infusion produces steady state, it is unclear whether a simple bolus can do the same. Given the relatively slow clearance of Gd, we hypothesized that a bolus technique accurately measures Ve, thus facilitating integration of myocardial fibrosis quantification into cardiovascular magnetic resonance (CMR) workflow routines. Assuming equivalence between techniques, we further hypothesized that Ve measures would be reproducible across scans.
  
  
  METHODS
  In 10 volunteers (ages 20-81, median 33 yr, 3 females), we compared serial Ve measures from a single short axis slice from two scans: first, during a constant infusion, and second, 12-50 min after a bolus (0.2 mmol/kg gadoteridol) on another day. Steady state during infusion was defined when serial blood and myocardial T1 data varied <5%. We measured T1 on a 1.5 T Siemens scanner using a single-shot modified Look Locker inversion recovery sequence (MOLLI) with balanced SSFP. To shorten breath hold times, T1 values were measured with a shorter sampling scheme that was validated with spin echo relaxometry (TR = 15 sec) in CuSO4-Agar phantoms. Serial infusion vs. bolus Ve measures (n = 205) from the 10 subjects were compared with generalized estimating equations (GEE) with exchangeable correlation matrices. LGE images were also acquired 12-30 minutes after the bolus.
  
  
  RESULTS
  No subject exhibited LGE near the short axis slices where Ve was measured. The Ve range was 19.3-29.2% and 18.4-29.1% by constant infusion and bolus, respectively. In GEE models, serial Ve measures by constant infusion and bolus did not differ significantly (difference = 0.1%, p = 0.38). For both techniques, Ve was strongly related to age (p < 0.01 for both) in GEE models, even after adjusting for heart rate. Both techniques identically sorted older individuals with higher mean Ve values.
  
  
  CONCLUSIONS
  Myocardial Ve can be measured reliably and accurately 12-50 minutes after a simple bolus. Ve measures are also reproducible across CMR scans. Ve estimation can be integrated into CMR workflow easily, which may simplify research applications involving the quantification of myocardial fibrosis.
authors.affiliation: Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. schelberteb@upmc.edu
authors.forename: Erik B
authors.initials: EB
authors.lastname: Schelbert
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Testa
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Meier
authors.forename: William J
authors.initials: WJ
authors.lastname: Ceyrolles
authors.forename: Joshua E
authors.initials: JE
authors.lastname: Levenson
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Blair
authors.forename: Peter
authors.initials: P
authors.lastname: Kellman
authors.forename: Bobby L
authors.initials: BL
authors.lastname: Jones
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Ludwig
authors.forename: David
authors.initials: D
authors.lastname: Schwartzman
authors.forename: Sanjeev G
authors.initials: SG
authors.lastname: Shroff
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Wong
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003198:Computer Simulation; D003287:Contrast Media / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005260:Female; D005355:Fibrosis; D005682:Gadolinium; D006331:Heart Diseases / Q000175:diagnosis* / Q000473:pathology; D006571:Heterocyclic Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008279:Magnetic Resonance Imaging / Q000295:instrumentation; D008297:Male; D009010:Monte Carlo Method; D009206:Myocardium / Q000473:pathology*; D009942:Organometallic Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010414:Pennsylvania; D019047:Phantoms, Imaging; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D057188:Workflow; D055815:Young Adult
chemical_list: D003287:Contrast Media; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; C062402:gadoteridol; D005682:Gadolinium